The woodchuck hepatitis virus (WHV) is taxonomically and serologically related to the hepatitis B virus (HBV). Infection with each of these viruses is associated with acute and chronic hepatitis and hepatic cell carcinoma in their respective hosts and these associations appear to be etiological in nature. Thus, WHV infection of woodchucks provides a relevant and convenient model for understanding HBV infections of humans. The following experiments were performed: (1) detection of WHV mutants in chronically infected woodchucks, (2) mutant WHV genomes in serum were found to resemble rearranged viral integrants in hepatocellular carcinoma, (3) analysis of the X gene promoter, (4) newly identified open reading frames of WHV are not essential for virus replication, (5) mutational analysis of the WHV X gene, and (6) analysis of a WHV mutant with a defective precore gene.